Liu Huailei, Li Chenguang, Shen Chen, Yin Fei, Wang Kaikai, Liu Yaohua, Zheng Bingjie, Zhang Weiguang, Hou Xu, Chen Xin, Wu Jianing, Wang Xiaoxiong, Zhong Chen, Zhang Jiakang, Shi Huaizhang, Ai Jing, Zhao Shiguang
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, No.23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang Province, People's Republic of China.
J Neurooncol. 2015 May;122(3):431-9. doi: 10.1007/s11060-015-1736-y. Epub 2015 Feb 27.
Glioblastoma multiforme (GBM) is the most malignant brain tumor in humans. Previous studies have demonstrated that microRNA plays important roles in the development and proliferation of GBM cells. Here we defined the mechanism by which miR-212-3p regulated the proliferation of GBM. In this study, we showed that miR-212-3p expression was significantly down-regulated and negatively correlated with serum and glucocorticoid-inducible kinase 3 (SGK3) in GBM. Either over-expression of miR-212-3p or silence of SGK3 decreased viability of GBM cells. Moreover, miR-212-3p directly bound to 3'UTR of SGK3 and inhibited its mRNA and protein expression. And over-expression of SGK3 rescued the decreased proliferation of GBM cells induced by miR-212-3p. Importantly, miR-212-3p also suppressed tumor growth in vivo. Collectively, our results demonstrated that miR-212-3p inhibited proliferation of GBM cells by directly targeting SGK3, and could potentially serve as a new therapeutic target for GBM.
多形性胶质母细胞瘤（GBM）是人类最恶性的脑肿瘤。先前的研究表明，微小RNA在GBM细胞的发育和增殖中起重要作用。在此，我们确定了miR-212-3p调控GBM增殖的机制。在本研究中，我们发现miR-212-3p的表达在GBM中显著下调，且与血清和糖皮质激素诱导激酶3（SGK3）呈负相关。miR-212-3p的过表达或SGK3的沉默均降低了GBM细胞的活力。此外，miR-212-3p直接与SGK3的3'UTR结合，抑制其mRNA和蛋白表达。SGK3的过表达挽救了miR-212-3p诱导的GBM细胞增殖减少。重要的是，miR-212-3p在体内也抑制肿瘤生长。总体而言，我们的结果表明，miR-212-3p通过直接靶向SGK3抑制GBM细胞增殖，并有可能成为GBM的新治疗靶点。
